摘要
目的:观察血府逐瘀胶囊通过调控沉默信息调节因子3(Sirt3)/鸟嘌呤核苷酸转化因子交换蛋白1(EPAC1)信号通路对高脂饲料诱导的动脉粥样硬化小鼠血脂、主动脉斑块的影响,探讨血府逐瘀胶囊改善动脉粥样硬化的作用机制。方法:将小鼠分为正常组,模型组,空白组,瑞舒伐他汀组,血府逐瘀胶囊低、中、高剂量组,正常组用C57BL/6J正常小鼠,其余各组为同品系载脂蛋白E敲除(ApoE^(-/-))小鼠。正常组和空白组常规饲养,其余各组采用高脂饲料喂养,连续24周构建小鼠动脉粥样硬化模型,血府逐瘀胶囊以0.3、0.6、1.2 g·kg^(-1)·d^(-1)剂量灌胃,瑞舒伐他汀组以0.05 g·kg^(-1)·d^(-1)剂量灌胃,正常组、模型组和空白组给予等体积去离子水灌胃,连续灌胃6周。采用小动物B超仪评估小鼠心功能和主动脉斑块情况;全自动生化分析仪检测小鼠总胆固醇(CHOL)、甘油三酯(TG)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)、极低密度脂蛋白(VLDL)等血脂指标;油红O染色观察主动脉脂质沉积情况;苏木素-伊红(HE)染色评估小鼠组织病理学改变;马松(Masson)染色观察小鼠血管内胶原沉积程度;透射电镜观察小鼠主动脉线粒体损伤情况;酶联免疫吸附测定法(ELISA)检测促肾上腺皮质激素(ACTH)、腺嘌呤核苷三磷酸(ATP)、烟碱型胆碱受体α1(CHRNα1)、总超氧化物歧化酶(T-SOD)等指标;实时荧光定量聚合酶链式反应(Real-time PCR)检测小鼠主动脉及心脏组织中Sirt3、EPAC1、胱天蛋白酶-3(Caspase-3)、B细胞淋巴瘤-2(Bcl-2)、Bcl-2关联X蛋白(Bax)mRNA相对表达;蛋白免疫印迹法(Western blot)检测Sirt3、EPAC1、Caspase-3、Bcl-2、Bax蛋白相对表达。结果:模型组主动脉弓多处形成动脉粥样硬化斑块,提示造模成功;经血府逐瘀胶囊治疗后,与模型组比较,斑块明显缩小,斑块数量也明显减少。生化结果显示,与正常组比较,模型组CHOL含量显�
Objective:To observe the effects of Xuefu Zhuyu capsules(XFZY)on blood lipid levels and aortic plaques in the mouse model of atherosclerosis(AS)induced by a high-fat diet by regulating the silencing regulatory factor 2-like protein 3(Sirt3)/exchange protein directly activated by cAMP 1(EPAC1)signaling pathway and explore the mechanism of XFZY in ameliorating AS.Method:Mice were assigned into normal,model,blank,rosuvastatin(0.05 g·kg^(-1)·d^(-1)),and low-,medium-,and high-dose(0.3,0.6,1.2 g·kg^(-1)·d^(-1),respectively)XFZY groups.The normal group consisted of normal C57BL/6J mice,while the other groups consisted of ApoE^(-/-)C57BL/6J mice.The normal group and blank group were fed routinely,and the rest groups were fed with a high-fat diet for 24 consecutive weeks for the modeling of AS.The drug intervention groups were administrated with corresponding drugs by gavage,and model group and blank group with an equal volume of deionized water for 6 consecutive weeks.The small animal B-ultrasound was used to evaluate the mouse heart function and aortic plaque condition.A fully automated biochemical analyzer was used to measure the levels of blood lipids such as total cholesterol(CHOL),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and extremely low-density lipoprotein(VLDL)in mice.Oil red O staining was employed to observe lipid deposition in the aorta.Hematoxylin-eosin staining and Masson staining were employed to observe the pathological changes and collagen deposition in mouse blood vessels.Transmission electron microscopy was employed to observe the mitochondrial damage in mouse aorta.The levels of adrenocorticotropic hormone(ACTH),adenosine triphosphate(ATP),and nicotinic choline receptorα1(CHRNα1),and total superoxide dismutase(T-SOD)were measured by enzyme-linked immunosorbent assay(ELISA).Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)and Western blot were performed to determine the mRNA and protein levels,respectively,o
作者
姚博
陈恒文
贡济宇
何轩辉
YAO Bo;CHEN Hengwen;GONG Jiyu;HE Xuanhui(School of Pharmaceutical Sciences,Changchun University of Chinese Medicine,Changchun 130117,China;Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2024年第21期31-41,共11页
Chinese Journal of Experimental Traditional Medical Formulae
基金
中国中医科学院科技创新工程重大攻关项目(CI2021A04619,CI2021A05011)
中央高水平中医医院临床科研业务费项目(HLCMHPP2023077)
中国中医科学院广安门医院续航人才工程青年拔尖人才培养项目(CZ40909)
国家自然科学基金项目(82205091)
中国中医科学院科技创新工程创新团队项目(CI2021B017-05)
河南省自然科学基金项目(232300420070)。
